Affinage

TROAP

Tastin · UniProt Q12815

Length
778 aa
Mass
83.9 kDa
Annotated
2026-06-10
26 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TROAP (tastin) is a proline-rich cytoplasmic protein with two well-supported roles: as an accessory factor in trophinin-mediated cell adhesion and as a microtubule-associated regulator of mitotic spindle architecture (PMID:9560222, PMID:12049630, PMID:18218922). In adhesion, TROAP does not bind trophinin directly but is bridged to it by bystin, an interaction enhanced by cytokeratins 8 and 18, enabling divalent cation-independent homophilic adhesion between trophoblastic and endometrial epithelial cells (PMID:7758945, PMID:9560222). TROAP associates with the microtubule cytoskeleton through its N-terminal basic region and directly binds the dynein light chain Tctex-1, co-sedimenting with polymerized microtubules and dispersing upon depolymerization (PMID:12049630). During mitosis its levels peak in G2/M, when it localizes to centrosomes and the spindle and interacts with dynein intermediate chain, the dynactin component p150(Glued), and gamma-tubulin; depletion produces multipolar spindles through pericentrosomal fragmentation and centriole splitting, while overexpression yields monopolar spindles, establishing TROAP as required for centrosome integrity and bipolar spindle assembly (PMID:18218922). Across multiple cancers TROAP acts as a proliferation- and invasion-promoting factor, binding DYRK1A/B to drive their cytoplasmic retention and activate Akt/GSK-3β signaling (PMID:33500384), physically associating with STAT3 (PMID:37298609), and operating within EZH2–TWIST/c-Myc (PMID:33692939) and Wnt/β-Catenin (PMID:34077623) programs. Its abundance is set transcriptionally by E2F1 activation (PMID:39501799) and KLF13 repression—the latter relieved by FBXW5-mediated ubiquitination of KLF13 (PMID:40696794)—and post-transcriptionally by METTL14-dependent m6A-driven mRNA destabilization (PMID:35251990) and PCBP2-mediated mRNA stabilization (PMID:39586843).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 Medium

    Established TROAP (tastin) as a cytoplasmic factor required for trophinin-mediated cell adhesion, defining its first biological context at the trophoblast-endometrial interface.

    Evidence Expression cDNA cloning and cell adhesion assays between HT-H and SNG-M cell lines

    PMID:7758945

    Open questions at the time
    • Did not resolve the molecular nature of the tastin-trophinin link
    • No structural or domain mapping of tastin's contribution
  2. 1998 High

    Resolved that tastin connects to trophinin indirectly, identifying bystin as the bridging protein and cytokeratins as a stabilizing component of the adhesion complex.

    Evidence Yeast two-hybrid, GST pulldown, and immunocytochemistry in HT-H cells

    PMID:9560222

    Open questions at the time
    • Did not establish stoichiometry or assembly order of the complex
    • Functional consequence of the cytokeratin enhancement not quantified in adhesion
  3. 2002 High

    Defined tastin as a microtubule-associated protein with an N-terminal microtubule-binding region and a direct dynein light chain (Tctex-1) interaction, linking it to the cytoskeletal transport machinery.

    Evidence Microtubule sedimentation, nocodazole treatment, deletion mutagenesis, yeast two-hybrid, Co-IP, GST-Tctex-1 pulldown

    PMID:12049630

    Open questions at the time
    • Cellular function of the Tctex-1 interaction not yet tested
    • Did not address mitotic role
  4. 2008 High

    Demonstrated that tastin is required for bipolar spindle assembly and centrosome integrity, connecting its dynein/microtubule associations to a concrete mitotic phenotype.

    Evidence siRNA knockdown, overexpression, immunofluorescence, Co-IP for dynein IC/p150(Glued)/gamma-tubulin, cell-cycle flow cytometry, Eg5 inhibition

    PMID:18218922

    Open questions at the time
    • Mechanism by which tastin maintains pericentrosomal material cohesion not defined
    • No structural model of the spindle-pole complex it participates in
  5. 2021 Medium

    Identified a cancer-promoting mechanism in which TROAP binds DYRK1A/B for cytoplasmic retention and activates Akt/GSK-3β to drive cell-cycle progression in hepatocellular carcinoma.

    Evidence Co-IP, shRNA/overexpression, tumor growth assays, Akt/GSK-3β western blot

    PMID:33500384

    Open questions at the time
    • Direct binding interface not mapped
    • Link to the mitotic centrosomal role unresolved
  6. 2021 Medium

    Placed TROAP within oncogenic transcriptional programs by showing it acts downstream of EZH2 to activate TWIST/c-Myc and upstream of Wnt/β-Catenin in distinct tumor types.

    Evidence shRNA knockdown with epistasis rescue (TWIST overexpression; β-Catenin/Axin2 silencing), Transwell, GSEA, western blot in prostate cancer and glioma cells

    PMID:33692939 PMID:34077623

    Open questions at the time
    • Direct molecular link between cytoplasmic TROAP and nuclear transcriptional output not defined
    • Effects shown as pathway epistasis rather than physical mechanism
  7. 2023 Medium

    Extended TROAP's oncogenic interactome by demonstrating a physical STAT3 interaction driving proliferation and metastasis in renal clear cell carcinoma.

    Evidence Co-IP with shotgun LC-MS/MS, functional rescue, xenograft

    PMID:37298609

    Open questions at the time
    • Interaction interface and effect on STAT3 phosphorylation not defined
    • Whether STAT3 binding is direct vs complex-mediated unresolved
  8. 2024 Medium

    Established multilayered regulation of TROAP abundance, identifying E2F1 as a direct transcriptional activator and PCBP2 as an mRNA-stabilizing RNA-binding protein.

    Evidence Dual luciferase reporter, RIP, actinomycin D stability assays, siRNA, rescue, xenografts in endometrial and gastric cancer

    PMID:39501799 PMID:39586843

    Open questions at the time
    • How these inputs are integrated in normal vs tumor cells unknown
    • PCBP2 binding site on TROAP mRNA not mapped
  9. 2025 Medium

    Defined additional regulatory and effector arms: KLF13 directly represses the TROAP promoter (relieved by FBXW5-driven KLF13 degradation), and TROAP promotes chemoresistance via de novo lipogenesis.

    Evidence ChIP, dual luciferase reporter, Co-IP, rescue, xenograft (KLF13/FBXW5); Nile red lipid staining and PI3K/Akt western blot (lipogenesis)

    PMID:40696794 PMID:41350492

    Open questions at the time
    • Lipogenesis link rests on staining and pathway blots without enzymatic reconstitution (Low confidence)
    • Whether the FBXW5-KLF13-TROAP axis operates outside lung adenocarcinoma untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TROAP's foundational microtubule/centrosome function mechanistically connects to its many cancer signaling and transcriptional roles remains unresolved.
  • No structural model of TROAP or its complexes
  • Unclear whether spindle/centrosome activity underlies the proliferative oncogenic phenotypes or is independent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 1
Complex memberships
trophinin-bystin-tastin adhesion complex

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Tastin (TROAP) is a cytoplasmic protein necessary for trophinin to function as a cell adhesion molecule; trophinin and tastin associate with the cytoskeleton and mediate divalent cation-independent homophilic cell adhesion between trophoblastic and endometrial epithelial cells at their apical surfaces. Expression cDNA cloning, cell adhesion assays between HT-H and SNG-M cell lines Genes & development Medium 7758945
1998 Tastin (TROAP) does not directly bind trophinin; instead, a third cytoplasmic protein, bystin, directly binds both trophinin and tastin, and this binding is enhanced by the presence of cytokeratin 8 and 18 as a third molecule. Tastin co-localizes with trophinin, bystin, and cytokeratins in HT-H cells. Yeast two-hybrid assays, in vitro protein binding assays (GST pulldown), immunocytochemistry Proceedings of the National Academy of Sciences of the United States of America High 9560222
2002 Tastin (TROAP) is a microtubule-associated protein; its N-terminal basic region mediates direct microtubule binding. Tastin co-sediments with polymerized microtubules and disperses to the cytoplasm upon nocodazole-induced microtubule depolymerization. Tastin also directly binds Tctex-1, a light chain of cytoplasmic dynein, as confirmed by yeast two-hybrid, co-immunoprecipitation, and in vitro GST-pulldown. Microtubule sedimentation assay, nocodazole treatment, N- and C-terminal deletion mutant analysis, yeast two-hybrid, co-immunoprecipitation, GST-Tctex-1 pulldown with in vitro translated tastin The Biochemical journal High 12049630
2008 Tastin (TROAP) is required for bipolar spindle assembly and centrosome integrity during mitosis. Tastin protein levels peak in G2/M phase. Tastin localizes to microtubules, centrosomes, and the mitotic spindle. Tastin interacts with dynein intermediate chain, p150(Glued) (dynactin component), and gamma-tubulin in addition to Tctex-1. Overexpression causes monopolar spindle formation; depletion causes multipolar spindles through fragmentation of pericentrosomal material and centriole splitting, exclusively during mitosis and dependent on microtubule integrity and Eg5 activity. Tastin depletion does not disrupt NuMA or p150(Glued) localization at spindle poles. siRNA knockdown, overexpression, immunofluorescence microscopy, co-immunoprecipitation, flow cytometry (cell cycle), nocodazole and Eg5-inhibitor treatment FASEB journal High 18218922
2021 TROAP directly binds DYRK1A/B, causing cytoplasmic retention of DYRK1A/B and promoting cell cycle progression via activation of Akt/GSK-3β signaling in hepatocellular carcinoma cells. Co-immunoprecipitation, shRNA knockdown, overexpression, in vitro and in vivo tumor growth assays, western blot for Akt/GSK-3β pathway Cell death & disease Medium 33500384
2021 In prostate cancer cells, TROAP functions downstream of EZH2 and activates the TWIST/c-Myc pathway to promote cell proliferation, migration, and invasion; overexpression of TWIST partially rescues the inhibitory effects of TROAP knockdown. Lentiviral shRNA knockdown, overexpression rescue assay, Transwell assay, flow cytometry, western blot, bioinformatic correlation analysis Frontiers in oncology Medium 33692939
2021 TROAP activates the Wnt/β-Catenin signaling pathway in glioma cells and promotes cell proliferation, migration, and invasion; silencing β-Catenin or Axin2 reverses the tumor-promoting effects of TROAP overexpression, placing TROAP upstream of Wnt/β-Catenin. shRNA knockdown, overexpression vector, epistasis rescue (β-Catenin/Axin2 silencing), CCK-8, colony formation, Transwell, flow cytometry, immunofluorescence, western blot, GSEA CNS neuroscience & therapeutics Medium 34077623
2022 METTL14-mediated m6A RNA methylation promotes TROAP mRNA degradation/instability; loss of METTL14 in ovarian cancer stabilizes TROAP mRNA and increases TROAP protein, promoting cancer cell proliferation. MeRIP-qPCR, RNA stability assay (actinomycin D), METTL14 overexpression, TROAP siRNA, luciferase reporter assay, cDNA microarray, immunohistochemistry Frontiers in oncology Medium 35251990
2023 TROAP physically interacts with STAT3 in kidney renal clear cell carcinoma cells to promote tumor proliferation, migration, and metastasis; this interaction was identified by co-immunoprecipitation followed by shotgun LC-MS and validated by functional rescue experiments. Co-immunoprecipitation, shotgun LC-MS/MS, qRT-PCR, western blot, Celigo, MTT, wound healing, flow cytometry, xenograft model, functional rescue assay International journal of molecular sciences Medium 37298609
2024 The transcription factor E2F1 directly activates TROAP transcription; E2F1 overexpression increases TROAP expression and promotes endometrial cancer cell proliferation, migration, and glycolysis in a TROAP-dependent manner. Dual luciferase reporter assay, qRT-PCR, western blot, siRNA knockdown, rescue experiments with TROAP knockdown, xenograft mouse model Histology and histopathology Medium 39501799
2024 PCBP2 (an RNA-binding protein) directly binds TROAP mRNA and stabilizes it in gastric cancer cells; PCBP2 depletion reduces TROAP mRNA half-life and suppresses GC cell proliferation, migration, invasion, and promotes ferroptosis. RIP (RNA immunoprecipitation) assay, actinomycin D RNA stability assay, siRNA knockdown, western blot, functional assays (EdU, wound healing, Transwell), xenograft model Naunyn-Schmiedeberg's archives of pharmacology Medium 39586843
2025 FBXW5 promotes ubiquitination-mediated degradation of KLF13; loss of KLF13 increases TROAP transcription (KLF13 suppresses TROAP promoter activity), thereby facilitating EMT in lung adenocarcinoma. TROAP overexpression reverses KLF13-mediated inhibition of invasion, migration, and EMT. Co-immunoprecipitation (FBXW5–KLF13 interaction), ChIP assay, dual luciferase reporter gene assay (KLF13 binding to TROAP promoter), overexpression rescue, western blot, Transwell, wound healing, CCK-8, xenograft Molecular carcinogenesis Medium 40696794
2025 TROAP promotes chemoresistance in colorectal cancer cells via de novo lipogenesis driven by histone acetylation and PI3K/Akt pathway activation, as evidenced by increased lipid droplet formation and altered PI3K/Akt signaling upon TROAP manipulation. Nile red staining (lipid droplet), western blot, flow cytometry, CCK-8, Transwell, proteomic and bioinformatics analysis, xenograft model Functional & integrative genomics Low 41350492

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation. Genes & development 156 7758945
1998 A cytoplasmic protein, bystin, interacts with trophinin, tastin, and cytokeratin and may be involved in trophinin-mediated cell adhesion between trophoblast and endometrial epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 89 9560222
1999 Expression of trophinin, tastin, and bystin by trophoblast and endometrial cells in human placenta. Biology of reproduction 62 10026108
1999 Trophinin, tastin, and bystin: a complex mediating unique attachment between trophoblastic and endometrial epithelial cells at their respective apical cell membranes. Seminars in reproductive endocrinology 56 10797941
2002 Human tastin, a proline-rich cytoplasmic protein, associates with the microtubular cytoskeleton. The Biochemical journal 51 12049630
2018 MicroRNA-519d-3p inhibits cell proliferation and migration by targeting TROAP in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 49 30021381
2008 Tastin is required for bipolar spindle assembly and centrosome integrity during mitosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 43 18218922
2021 TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression. Cell death & disease 31 33500384
2019 TROAP Promotes Breast Cancer Proliferation and Metastasis. BioMed research international 28 31198787
2018 Decreased expression of TROAP suppresses cellular proliferation, migration and invasion in gastric cancer. Molecular medicine reports 28 29956806
2018 TROAP regulates prostate cancer progression via the WNT3/survivin signalling pathways. Oncology reports 27 30431120
2022 Downregulation of Methyltransferase-Like 14 Promotes Ovarian Cancer Cell Proliferation Through Stabilizing TROAP mRNA. Frontiers in oncology 25 35251990
2021 TROAP regulates cell cycle and promotes tumor progression through Wnt/β-Catenin signaling pathway in glioma cells. CNS neuroscience & therapeutics 25 34077623
2000 Recent molecular approaches to elucidate the mechanism of embryo implantation: trophinin, bystin, and tastin as molecules involved in the initial attachment of blastocysts to the uterus in humans. Seminars in reproductive medicine 25 11299965
2021 MiR-532-3p suppresses cell viability, migration and invasion of clear cell renal cell carcinoma through targeting TROAP. Cell cycle (Georgetown, Tex.) 19 34287099
2021 EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals. Frontiers in oncology 13 33692939
2023 TROAP Promotes the Proliferation, Migration, and Metastasis of Kidney Renal Clear Cell Carcinoma with the Help of STAT3. International journal of molecular sciences 12 37298609
2023 Tastin promotes non-small-cell lung cancer progression through the ErbB4, PI3K/AKT, and ERK1/2 pathways. Experimental biology and medicine (Maywood, N.J.) 10 36691332
2023 METTL3 regulatory TROAP can regulate the progression of non-small cell lung cancer through PI3K/AKT and EMT signaling pathway. Medical oncology (Northwood, London, England) 8 37608033
2023 Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma. MedComm 8 37731946
2024 E2F1-induced upregulation of TROAP contributes to endometrial cancer progression. Histology and histopathology 4 39501799
2025 FBXW5 Promotes Epithelial-Mesenchymal Transition in Lung Adenocarcinoma Through the KLF13/TROAP Signaling Pathway. Molecular carcinogenesis 1 40696794
2025 TROAP aggravates chemoresistance of colorectal cancer cells via lipogenesis by PI3K/Akt pathway and histone acetylation. Functional & integrative genomics 1 41350492
2024 PCBP2 stabilizes TROAP to promote the malignant progression of gastric cancer. Naunyn-Schmiedeberg's archives of pharmacology 1 39586843
2025 TROAP promotes esophageal squamous cell carcinoma progression via the PI3K/AKT pathway. Journal of cancer research and clinical oncology 0 40252097
2024 LncRNA ERICD interacts with TROAP to regulate TGF-β signaling in hepatocellular carcinoma. Heliyon 0 39148975

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